Forming 3-D nano-particle assemblies

ABSTRACT

According to an example, methods for forming three-dimensional (3-D) nano-particle assemblies include depositing SES elements onto respective tips of nano-fingers, in which the nano-fingers are arranged in sufficiently close proximities to each other to enable the tips of groups of adjacent ones of the nano-fingers to come into sufficiently close proximities to each other to enable the SES elements on the tips to be bonded together when the nano-fingers are partially collapsed. The methods also include causing the nano-fingers to partially collapse toward adjacent ones of the nano-fingers to cause a plurality of SES elements on respective groups of the nano-fingers to be in relatively close proximities to each other and form respective clusters of SES elements, introducing additional particles that are to attach onto the clusters of SES elements, and causing the clusters of SES elements to detach from the nano-fingers.

BACKGROUND

In surface-enhanced spectroscopy (SES), such as surface-enhanced Ramanspectroscopy (SERS), vibrationally or electronically excitable levels ofan analyte are probed. The energy of a photon can shift by an amountequal to that of the vibrational level excited by the photon (Ramanscattering). A Raman spectrum, which consists of a wavelengthdistribution of bands corresponding to molecular vibrations specific tothe analyte being probed, may be detected to identify the analyte. InSERS, the analyte molecules are in close proximity, for instance, lessthan tens of nanometers, to metal nano-particles that may be or may notbe coated with a dielectric, such as silicon dioxide, silicon nitride,and a polymer, that, once excited by light, set up plasmon modes, whichcreate near fields around the metal nano-particles. These fields cancouple to analyte molecules in the near field regions. As a result,concentration of the incident light occurs at close vicinity to thenano-particles, enhancing the emission of scattered signals from theanalyte molecules.

BRIEF DESCRIPTION OF THE DRAWINGS

Features of the present disclosure are illustrated by way of example andnot limited in the following figure(s), in which like numerals indicatelike elements, in which:

FIG. 1A shows an isometric view of an apparatus for formingthree-dimensional (3-D) nano-particle assemblies, according to anexample of the present disclosure;

FIGS. 1B and 1C, respectively show cross-sectional views along a lineA-A of the apparatus shown in FIG. 1A, prior to and following partialcollapse of the nano-fingers contained in the apparatus, according toexamples of the present disclosure;

FIGS. 1D and 1E, respectively show diagrams of various exampleconfigurations of SES elements, and in some instances, bindingmolecules, according to various examples of the present disclosure;

FIG. 2 shows a flow diagram of a method for forming 3-D nano-particleassemblies, according to an example of the present disclosure; and

FIGS. 3A-3C, 4A-4C, 5A-5C, 6A-6B, 7A-7B, 8A-8C, and 9A-9C, respectivelyshow diagrams of various stages of methods for forming 3-D nano-particleassemblies, according to examples of the present disclosure.

DETAILED DESCRIPTION

For simplicity and illustrative purposes, the present disclosure isdescribed by referring mainly to an example thereof. In the followingdescription, numerous specific details are set forth in order to providea thorough understanding of the present disclosure. It will be readilyapparent however, that the present disclosure may be practiced withoutlimitation to these specific details. In other instances, some methodsand structures have not been described in detail so as not tounnecessarily obscure the present disclosure.

Throughout the present disclosure, the terms “a” and “an” are intendedto denote at least one of a particular element. As used herein, the term“includes” means includes but not limited to, the term “including” meansincluding but not limited to. The term “based on” means based at leastin part on. In addition, the term “light” refers to electromagneticradiation with wavelengths in the visible and non-visible portions ofthe electromagnetic spectrum, including infrared, near infrared, andultra-violet portions of the electromagnetic spectrum.

Disclosed herein are methods for forming three-dimensional (3-D)nano-particle assemblies and 3-D nano-particle assemblies that may beformed through implementation of the methods. As described in greaterdetail herein below, the methods may include the use of a plurality ofnano-fingers onto which a plurality of surface-enhanced spectroscopy(SES) elements may be deposited. Through partial collapsing of thenano-fingers onto other ones of the nano-fingers, for instance, in acontrolled manner, the SES elements positioned on various groups of thenano-fingers may be brought into sufficiently close proximities toenable those SES elements to be bonded together in a designed geometry.In one regard, the use of the nano-fingers in bonding respective groupsof SES elements together generally enables the groups of SES elements tobe arranged in relatively tighter packed configurations than may bepossible with conventional methods of SES element bonding.

Following bonding of the respective groups of SES elements to each otherto form respective clusters, additional particles that are to attachonto the clusters may be introduced. The additional particles may beattached to the clusters to form the 3-D nano-particle assembliesdisclosed herein. Additionally, a reporter molecule may be trappedbetween the SES elements as they are formed into the clusters. In someexamples, the reporter molecule may be a binding molecule that is tobond the SES elements in the clusters.

According to an example, protective coatings may be provided on surfacesof the 3-D nano-particle assemblies disclosed herein. In addition, theprotective coatings may be functionalized to preferentially bond tospecific regions, e.g., target tissues/cells in a human body. Thus, forinstance, the 3-D nano-particle assemblies disclosed herein may beemployed to map locations of the specific regions.

Generally speaking, conventional Raman based tagging structures aretypically composed of a Raman reporter molecule trapped in the “hotspot” of plasmonic nano-particle assemblies that typically havetwo-dimensional dimer or trimer structures. A similar configuration maybe used for fluorescence reporter molecules. When the hot spot isexcited by laser light of the appropriate wavelength, the reportermolecule may emit a signature radiation pattern that is enhanced due toits location in the hot spot. These hot spots typically have a strongpolarization dependence, particularly in the dimer structures mostcommonly used. However, the excitation light source is typicallyrandomly polarized, and conventional tagging structures are alsorandomly oriented. As such, because of the strong polarizationdependence, the use of conventional tagging structures often results inweak signals and low contrast.

The 3-D nano-particle assemblies disclosed herein may be substantiallyless dependent upon the polarization of the excitation light and theorientations of the 3-D nano-particle assemblies as compared withconventional tagging structures. In addition, or alternatively, the 3-Dnano-particle assemblies disclosed herein may be fabricated to havepredetermined polarization attributes that, for instance, maysubstantially be aligned with the excitation light. In any regard,therefore, the 3-D nano-particle assemblies disclosed herein may be ableto achieve relatively stronger enhancement and thus better imaging ascompared with conventional tagging structures. In addition, throughimplementation of the forming methods disclosed herein, the 3-Dnano-particle assemblies disclosed herein may be formed to havesubstantially uniform configurations with respect to each other. Thesubstantial uniformity of the 3-D nano-particle assemblies may alsoresult in more consistent enhancement and thus more consistent detectionas compared with 3-D particle assemblies having random configurations.In another regard, therefore, the methods disclosed herein may beimplemented to engineer 3-D particle assemblies having specificgeometries that significantly enhance signal emissions from, forinstance, the reporter molecules contained in the 3-D particleassemblies.

With reference first to FIGS. 1A-1C, there are respectively shown anisometric view and cross-sectional views taken along lines A-A of FIG.1A of an apparatus 100 for forming three-dimensional (3-D) nano-particleassemblies, according to an example. It should be understood that theapparatus 100 depicted in FIGS. 1A-1C may include additional componentsand that some of the components described herein may be removed and/ormodified without departing from a scope of the apparatus 100 disclosedherein. It should also be understood that the components depicted inFIGS. 1A-1C are not drawn to scale and thus, the components may havedifferent relative sizes with respect to each than as shown therein.

An example of a 3-D nano-particle assembly that may be formed throughimplementation of the apparatus 100 may include a base cluster ofsurface-enhanced spectroscopy (SES) elements 106 on which an additionalparticle, such as a functional molecule or another base cluster of SESelements 106, may be attached. The base cluster of SES elements 106 maybe attached to each other substantially along the first plane and theadditional particle may be attached to the base cluster of SES elements106 on a second plane that is different from the first plane, therebyforming the 3-D nano-particle assembly.

As shown in FIG. 1A, the apparatus 100 includes a substrate 102, whichmay be formed of a material, such as, silicon, silicon nitride, glass,plastic, polymer, SiO₂, Al₂O₃, aluminum, etc., or a combination of thesematerials, etc. In addition, a plurality of nano-fingers 104 aredepicted as extending above a surface of the substrate 102 and aplurality of SES elements 106 are depicted as being positioned on thetips of respective nano-fingers 104.

According to an example, the nano-fingers 104 may have dimensions thatare in the nanometer range, for instance, dimensions that may be lessthan about 500 nm, and may be formed of a relatively flexible materialto enable the nano-fingers 104 to be laterally bendable or collapsible,for instance, to enable tips of the nano-fingers 104 to move toward eachother, as discussed in greater detail herein below. Examples of suitablematerials for the nano-fingers 104 may include polymer materials, suchas, UV-curable or thermal curable imprinting resist, polyalkylacrylate,polysiloxane, polydimethylsiloxane (PDMS) elastomer, polyimide,polyethylene, polypropelene, polyurethane, fluoropolymer, etc., or anycombination thereof, metallic materials, such as, gold, silver,aluminum, etc., semiconductor materials, etc., and combinations thereof.

The nano-fingers 104 may be attached to the surface of the substrate 102through any suitable attachment mechanism. For instance, thenano-fingers 104 may be grown directly on the substrate 102 surfacethrough implementation of any of a variety of suitable nano-structuregrowing techniques. As another example, the nano-fingers 104 may beintegrally formed with the substrate 102. In this example, for instance,a portion of the material from which the substrate 102 is fabricated maybe etched or otherwise processed to form the nano-fingers 104. In afurther example, a separate layer of material may be adhered to thesubstrate 102 surface and the separate layer of material may be etchedor otherwise processed to form the nano-fingers 104. In variousexamples, the nano-fingers 104 may be fabricated through ananoimprinting or an embossing process in which a template of relativelyrigid pillars may be employed in a multi-step imprinting process on apolymer matrix to form the nano-fingers 104. In these examples, atemplate may be formed through photolithography or other advancedlithography with the desired patterning to arrange the nano-fingers 104in the predetermined arrangement. More particularly, for instance, thedesired patterns may be designed on a mold by any of E-beam lithography,photolithography, laser interference lithography, Focused Ion Beam(FIB), self-assembly of spheres, etc. In addition, the pattern may betransferred onto another substrate, for instance, a silicon, glass, orpolymer substrate (polydimethylsiloxane (PDMS), polyimide,polycarbonate, etc.). Various other processes, such as, etching, andvarious techniques used in the fabrication of micro-electromechanicalsystems (MEMS) and nano-electromechanical systems (NEMS) may also beused to fabricate the nano-fingers 104.

The nano-fingers 104 have been depicted as having substantiallycylindrical cross-sections. It should, however, be understood that thenano-fingers 104 may have other shaped cross-sections, such as, forinstance, rectangular, square, triangular, etc. In addition, oralternatively, the nano-fingers 104 may be formed with a feature, suchas, notches, bulges, etc., to substantially cause the nano-fingers 104to be inclined to collapse in particular directions. Thus, for instance,two or more adjacent nano-fingers 104 may include features to increasethe likelihood that the nano-fingers 104 collapse toward each other.According to a particular example, groups of three or more adjacentnano-fingers 104 include features or may otherwise be fabricated tocollapse toward each other, such that the tips on the three or moreadjacent nano-fingers 104 may come into close contact with each otherwhen the nano-fingers 104 are partially collapsed. Various manners inwhich the nano-fingers 104 may be partially collapsed are described ingreater detail herein below.

The apparatus 100 includes a substantially random distribution ofnano-fingers 104 or a predetermined configuration of nano-fingers 104.In any regard, according to an example, the nano-fingers 104 may bearranged with respect to each other such that the tips of at least twoneighboring nano-fingers 104 are able to be brought into close proximitywith each other when the nano-fingers 104 are in a partially collapsedstate. By way of particular example, the neighboring nano-fingers 104may be positioned less than about 100 nanometers apart from each other.According to a particular example, the nano-fingers 104 may be patternedon the substrate 102 such that neighboring ones of the nano-fingers 104preferentially partially collapse into predefined geometries, forinstance, triangles, squares, pentagons, etc. In this regard, the numberof SES elements 106 being formed into respective clusters 112 maysubstantially be controlled through control of the patterning of thenano-fingers 104.

Turning now to FIG. 1B, there is shown a cross-sectional view along aline A-A in FIG. 1A of the apparatus 100, in accordance with an example.As shown therein, each of the tips 108 of the nano-fingers 104 includesa respective SES element 106 disposed thereon. The SES elements 106,which may include metallic nanoparticles as discussed below, may bedeposited onto the tips 108 of the nano-fingers 104 through one of, forinstance, physical vapor deposition (PVD), chemical vapor deposition(CVD), sputtering, etc., of metallic material, or self-assembly ofpre-synthesized nano-particles.

Generally speaking, the SES elements 106 may be elements that enhancethe emission of any of light, fluorescence, luminescence, etc., byparticles in relatively close proximities to the SES elements 106 andtherefore enhance sensing operations, such as surface enhanced Ramanspectroscopy (SERS), enhanced photoluminescence, enhanced fluorescence,etc., on the particles. The SES elements 106 may include plasmonicnanoparticles or nanostructures, which may be plasmon-supportingmaterials such as but not limited to, gold (Au), silver (Ag), and copper(Cu).

The SES elements 106 may have nanoscale surface roughness, which maygenerally be characterized by nanoscale surface features on the surfaceof the layer(s) and may be produced spontaneously during deposition ofthe plasmon-supporting material layer(s). By definition herein, aplasmon-supporting material may be a material that facilitatesscattering of signals and the production or emission of a signal from ananalyte on or near the material during spectroscopy.

In some examples, the SES elements 106 may be functionalized tofacilitate adsorption of target molecules. For example, surfaces of theSES elements 106 may be functionalized such that a particular class ofanalytes may be attracted to and may bond or be preferentially adsorbedonto the SES elements 106. By way of particular example, the SESelements 106 may be functionalized to attach to target molecules thatmay be contained in, for instance, particular types of cells, tissues,etc.

Although the nano-fingers 104 have been depicted in FIGS. 1A-1B as eachextending vertically and at the same heights with respect to each other,it should be understood that some of the nano-fingers 104 may extend atvarious angles and heights with respect to each other. The differencesin angles and/or heights between the nano-fingers 104 may occur, forinstance, due to differences arising from manufacturing or growthvariances existent in the fabrication of the nano-fingers 104 and thedeposition of the SES elements 106 on the nano-fingers 104, etc.

As shown in FIG. 1B, the nano-fingers 104 are in a first position, inwhich the tips 108 are in a substantially spaced arrangement withrespect to each other. The gaps 110 between the tips 108 may be ofsufficiently large size to enable a liquid to be positioned in the gaps110. In addition, the gaps 110 may be of sufficiently small size toenable the tips 108 of at least some of the nano-fingers 104 to be drawntoward each other as the liquid provided in the gaps 110 evaporates,through, for instance, capillary forces applied on the tips 108 as theliquid evaporates.

Turning now to FIG. 1C, there is shown a cross-sectional view along aline A-A, shown in FIG. 1A, of the apparatus 100, following evaporationof the liquid, according to an example. The view depicted in FIG. 1C isidentical to the view depicted in FIG. 1B, except that the nano-fingers104 are depicted in a second position, in which the tips 108 of some ofthe nano-fingers 104 have been drawn toward with each other. Accordingto an example, the tips 108 of some of the nano-fingers 104 may be inand may remain in relatively close proximity to each other for a periodof time due to the capillary forces applied on adjacent ones of thenano-fingers 104 during and following evaporation of the liquid (notshown) in the gaps 110 between the tips 108.

In one regard, the partial collapse of the nano-fingers 104 may causethe SES elements 106 positioned on the adjacent tips 108 of thenano-fingers 104 that have partially collapsed toward each other to comeinto relatively close proximities with respect to each other and in someinstances, to contact each other. According to an example, the SESelements 106 may include gold and the contacting SES elements 106 maybond to each other through gold-gold bonding. According to anotherexample, the SES elements 106 may include any of gold, silver, platinum,etc., and the SES elements 106 that are on adjacent tips 108 of thenano-fingers 104 may bond to each other through binding molecules 120,such as dithiol, diamine, etc. In this example, the fluid that may beused to partially collapse the nano-fingers 104 may include a solutioncontaining the binding molecules 120, such that the binding molecules120 may bind the SES elements 106 that are in relatively closeproximities to each other, i.e., SES elements 106 on adjacent tips 108of a group of partially collapsed nano-fingers 104.

As also shown in FIG. 1C, the SES elements 106 may be formed intoclusters 112 of SES elements 106. In some examples, the SES elements 106and the binding molecules 120 may collectively be formed into theclusters 112. According to an example, the binding molecules 120 may bereporter molecules, such as Raman tags, fluorescence tags, etc. By wayof particular example, the binding molecules 120 may be4,4′-thiobisbenzenethiol (TBBT) tags. In other examples, the reportermolecules may be separate molecules that may be trapped between the SESelements 106 in the clusters 112.

Turning now to FIGS. 1D and 1E, there are shown diagrams of variousexample configurations of the SES elements 106, and in some instances,the binding molecules 120, according to various examples. Generallyspeaking, the diagrams depicted in FIGS. 1D and 1E illustrate examplesof possible arrangements of the SES elements 106 (and the bindingmolecule 120) that may result when the nano-fingers 104 are partiallycollapsed as shown in FIG. 1C. It should thus be understood that thediagrams depicted in FIGS. 1D and 1E are provided merely for purposes ofillustration and that therefore any number of alternate configurations,which may include other numbers of SES elements 106 and/or bindingmolecules 120, may be formed without departing from scopes of examplesof the present disclosure.

With reference first to FIG. 1D, the first diagram 130 illustrates anexample in which three SES elements 106 may be bonded together, forinstance, through gold-gold bonding, to form the cluster 112. The seconddiagram 132 illustrates an example in which three SES elements 106 maybe bonded together through binding molecules 120 to form the cluster112, and in which the SES elements 106 do not contact each other.

With reference now to FIG. 1E, the first diagram 140 illustrates anexample in which five SES elements 106 may be bonded together, forinstance, through gold-gold bonding, to form the cluster 112. The seconddiagram 142 illustrates an example in which five SES elements 106 may bebonded together through binding molecules 120 to form the cluster 112.Additionally, in a cluster 112, some of the SES elements 106 may bebonded to each other through gold-gold bonding while others of the SESelements 106 may be bonded to each other through binding molecules 120.

Turning now to FIG. 2, there is shown a flow diagram of a method 200 forforming three-dimensional (3-D) nano-particle assemblies, according toan example. It should be understood that the method 200 depicted in FIG.2 may include additional processes and that some of the processesdescribed herein may be removed and/or modified without departing from ascope of the method 200.

At block 202, a plurality of SES elements 106 may be deposited onto thetips 108 of a plurality of nano-fingers 104, in which the plurality ofnano-fingers 104 extend from a substrate 102 and may be arranged insufficiently close proximities to each other to enable the tips 108 ofgroups of adjacent ones of the plurality of nano-fingers 104 to comeinto sufficiently close proximities to each other to enable the SESelements 106 on the tips 104 to be bonded together when the nano-fingers104 are partially collapsed. That is, the plurality of nano-fingers 104may be in sufficiently close proximities to each other to enable the SESelements 106 on the tips 104 of respective groups of nano-fingers 104,for instance, three or more, to be bonded to each other through eitheror both of gold-gold bonding and binding molecules 120.

At block 204, the nano-fingers 104 may be caused to partially collapsetoward adjacent ones of the nano-fingers to cause the SES elements 106on respective groups of the nano-fingers 104 to be in relatively closeproximities to each other and form respective clusters 112 of SESelements 106. As discussed above, the nano-fingers 104 may be fabricatedon the substrate 102 such that the nano-fingers 104 in respective groupspartially collapse toward each other (and thus not toward nano-fingers104 in other groups). As also discussed above, the nano-fingers 104 maybe caused to partially collapse toward each other through introductionand removal of a fluid between the nano-fingers 104.

At block 206, additional particles that are to attach onto the clustersof SES elements may be introduced onto the clusters 112 of SES elements106. As described in greater detail below, the additional particles maybe introduced onto the clusters 112 of SES elements 106 while theclusters 112 of SES elements 106 may be on the tips 108 of thenano-fingers 104. In other examples, the additional particles may beintroduced onto the clusters 112 following detachment of the clusters112 from the tips 108 of the nano-fingers 104. The additional particlesmay bond with the clusters 112 to form the 3-D nano-particle assembliesas discussed in greater detail below.

At block 208, the clusters 112 of SES elements 106 may be caused todetach from the tips 108 of the nano-fingers 104. The clusters 112 ofSES elements 106 may be caused to detach from the tips 108 of thenano-fingers 104 in a variety of manners, various examples of which aredescribed below. In addition, the 3-D nano-particle assemblies may beformed before, during, and/or after detachment of the clusters 112 asdiscussed with respect to the following examples.

Turning now to FIGS. 3A-3C, there are respectively shown diagrams 300,302, 304 of various stages of a method for forming 3-D nano-particleassemblies 320, according to an example. As shown in the diagram 300,additional particles, in this example, a plurality of protective coatingparticles 306, may be introduced onto the clusters 112 of SES elements106. The protective coating particles 306 may be introduced onto theclusters 112 through any suitable deposition technique, such as throughspraying of the protective coating particles 306, through implementationof an inkjet-like apparatus, etc.

According to an example, the protective coating particles 306 mayinclude silicon oxide or other type of oxide. In addition, theprotective coating particles 306 may combine to form a protectivecoating 308 on the exposed sides of the clusters 112 as half-shells ofprotective coatings 308 on the clusters 112 as shown in the diagram 302in FIG. 3B. The diagram 302 also shows that the clusters 112, along withthe protective coatings 308, may be detached from the nano-fingers 104,as denoted by the arrows 309. The diagram 302 further shows that thebottoms of SES elements 106 that were in contact with the tips 108 ofthe nano-fingers 104 may be exposed in the detached clusters 112.Although not shown in FIG. 3B, the clusters 112 may be released into asolution.

As shown in the diagram 304, linker molecules 310 may be introduced ontothe clusters 112. The linker molecules 310 may include any suitable typeof molecule that is to link SES elements 106 together. By way ofexample, the linker molecules 310 may be dithiol, diamine, etc. As shownin the diagram 304 (FIG. 3C), the linker molecules 304 may link theexposed portions of multiple clusters 112 to form 3-D nano-particleassemblies 320. According to an example, the 3-D nano-particleassemblies 320 may be implemented in biological imaging application, inwhich the protective coating 308 may protect the clusters 112 of SESelements 106 during and after insertion of the 3-D nano-particleassemblies 320 in a sample, such as a human body. In addition, anadditional material (not shown) may be applied onto the protectivecoating 308 and/or the protective coating 308 may otherwise befunctionalized to attach to target molecules inside of the sample.According to an example, the protective coating 308 may protect the SESelements 106 from various materials contained in the sample, such as,certain proteins, cells, etc. In this regard, although the 3-Dnano-particle assemblies 320 have been depicted as having gaps betweenthe clusters 112, the linker molecules 310 may bond the clusters 112with a relatively small gap therebetween to substantially prevent thematerials in the sample from contacting the SES elements 106.

Turning now to FIGS. 4A-4C, there are respectively shown diagrams 400,402, 404 of various stages of a method for forming 3-D nano-particleassemblies 410, according to an example. As shown in the diagram 400(FIG. 4A), additional particles, in this example, functional particles406, may be introduced onto the clusters 112 of SES elements 106.According to an example, the functional particles 406 may be particlesthat are similar to the SES elements 106. In another example, thefunctional particles 406 may be particles that are to afford otherfunctions to the 3-D nano-particle assemblies 410. By way of example,the functional particles 406 may be functionalized to attach to targetmolecules that may be contained in, for instance, particular types ofcells, tissues, etc.

In any regard, the functional particles 406 are depicted in the diagram400 as including a particular electrical charge, in this case a negativeelectrical charge. In addition, the apparatus 100 is depicted asincluding an electrically conductive layer 408 provided on the substrate102. Moreover, an oppositely biased electrical charge, in this case apositive electrical charge, may be applied on the clusters 112 of SESelements 106 when a voltage is applied through the electricallyconductive layer 408. The opposite biases of the functional particles406 and the clusters 112 of SES elements 106 may generally cause thefunctional particles 406 to be attracted to and contact the clusters 112of SES elements 106. The functional particles 406 may also bond with theSES elements 106 through gold-gold bonding, a binding molecule, and/orthrough an electrostatic force that may remain between the functionalparticles 406 and the SES elements 106 following cessation of theapplied voltage on the electrically conductive layer 408.

As shown in the diagram 402 (FIG. 4B), the combinations of thefunctional particles 406 and the respective clusters 112 may form the3-D nano-particle assemblies 410. In addition, as shown in the diagram404 (FIG. 4C), the 3-D nano-particle assemblies 410 may be caused to bedetached from the nano-fingers 104, as denoted by the arrows 409. The3-D nano-particle assemblies 410 may be caused to be detached from thenano-fingers 104 through any suitable detachment techniques, some ofwhich are described below.

Turning now to FIGS. 5A-5C, there are respectively shown diagrams 500,502, 504 of various stages of a method for forming 3-D nano-particleassemblies 510, according to an example. As shown in the diagram 500(FIG. 5A), additional particles, in this example, magnetic particles506, may be introduced onto the clusters 112 of SES elements 106.According to an example, the magnetic particles 506 may be particlesthat are similar to the SES elements 106. In another example, themagnetic particles 506 may be particles that are to afford otherfunctions to the 3-D nano-particle assemblies 510. By way of example,the magnetic particles 506 may be functionalized to attach to targetmolecules that may be contained in, for instance, particular types ofcells, tissues, etc.

The magnetic particles 506 may be particles that are entirely magneticor particles having magnetic cores and shells that may be non-magnetic.For instance, the magnetic particles 506, or the cores thereof, mayinclude magnetic materials, such as, nickel, iron, cobalt, gadolinium,etc. In instances where the magnetic particles 506 include magneticcores, the shells thereof may include a material and may befunctionalized in manners similar to the SES elements 106 and may thusinclude, for instance, gold, silver, copper, etc. In addition, the SESelements 106 may have similar configurations, e.g., magnetic coressurrounded by functionalized shells.

In any regard, the magnetic particles 506 may be attracted to the SESelements 106 and may contact the SES elements 106 due the magneticforces of both the SES elements 106 and the magnetic particles 506. Themagnetic forces may substantially be enhanced through application of avoltage through the electrically conductive layer 508, which may causean electromagnetic force to be generated around the SES elements 106.The magnetic particles 506 may also bond with the SES elements 106through gold-gold bonding or a binding molecule 120.

As shown in the diagram 502 (FIG. 5B), the combinations of the magneticparticles 506 and the respective clusters 112 may form the 3-Dnano-particle assemblies 510. In addition, as shown in the diagram 504(FIG. 5C), the 3-D nano-particle assemblies 510 may be caused to bedetached from the nano-fingers 104, as denoted by the arrows 509. The3-D nano-particle assemblies 510 may be caused to be detached from thenano-fingers 104 through any suitable detachment techniques, some ofwhich are described below.

Turning now to FIGS. 6A and 6B, there are respectively shown diagrams600 and 602 of various stages of a method for forming 3-D nano-particleassemblies 610, according to an example. As shown in the diagram 600(FIG. 6A), additional particles 604 are depicted as having bonded withthe clusters 112 to form 3-D nano-particle assemblies 610. Theadditional particles 604 may be bonded to the clusters 112 in any of themanners discussed above. In this regard the 3-D nano-particle assemblies610 may include any of the 3-D nano-particle assemblies 410 and 510discussed above with respect to FIGS. 4A-5C.

In addition, the apparatus 100, along with the 3-D nano-particleassemblies 610, are depicted as being positioned in a solution 606. Thesolution 606 may include any suitable type of material into which the3-D nano-particle assemblies 610 may be released. Thus, for instance,the solution 606 may include a material that does not interact with oradversely affect the 3-D nano-particle assemblies 610. In any regard, asalso shown in the diagram 600, a vibration 608 may be applied onto theapparatus 100. The vibration 608 may include a sonication appliedthrough the solution 606 and/or a physical vibration of the application100. Although not shown, the vibration 608 may be generated through anyconventional vibration source suitable to generate sufficient vibrationsto cause the 3-D nano-particle assemblies 610 to be detached from thenano-fingers 104. As shown in the diagram 602 (FIG. 6B), the vibration608 is intended to cause the 3-D nano-particle assemblies 610 to bedetached from the nano-fingers 104 and released into the solution 606 asdenoted by the arrows 609.

According to an example, a layer of material may be provided on the tips108 of the nano-fingers 104 to enhance release of the 3-D nano-particleassemblies 610 from the nano-fingers 104. The material may include, forinstance, a fluorocarbon.

Turning now to FIGS. 7A and 7B, there are respectively shown diagrams700 and 702 of various stages of a method for forming 3-D nano-particleassemblies 610, according to an example. The diagrams 700 and 702 arerespectively similar to the diagrams 600 and 602 and thus, featureshaving the same reference numerals will not be discussed with respect toFIGS. 7A and 7B. The diagrams 700 and 702 differ from the diagrams 600and 602 in that, in the diagrams 700 and 702, a vibration 608 may not beapplied onto the 3-D nano-particle assemblies 610. Instead, in thediagram 700, a sacrificial layer 704 is depicted as being providedbetween the tips 108 of the nano-fingers 104 and the clusters 112.

The sacrificial layer 704 may be deposited onto the tips 108 of thenano-particles 104 prior to deposition of the SES elements 106.Additionally, the sacrificial layer 704 may be deposited onto the tips108 in any of the manners discussed above with respect to the depositionof the SES elements 106, or using alternative techniques such as spincoating or other standard microfabrication processes.

The apparatus 100 along with the 3-D nano-particle assemblies 610, aredepicted as being positioned in a solution 706. The solution 706 mayinclude any suitable type of material into which the 3-D nano-particleassemblies 610 may be released. In addition, the solution 706 may be asolution that is to dissolve the sacrificial layer 704 and may beselected based upon the materials with which the sacrificial layer 704may be formed. By way of particular examples, the sacrificial layer 704may include aluminum (Al) and the solution 706 may include dilutehydrochloric acid (HCl) solution, the sacrificial layer 704 may includetitanium (Ti) and the solution 706 may include dilute hydrofluoric acid(HF), the sacrificial layer 704 may include polymethyl methacrylate(PMMA) and the solution 706 may include a solvent, etc. In any regard,as shown in the diagram 702 (FIG. 7B), the sacrificial layer 704 is tobe dissolved thereby causing the 3-D nano-particle assemblies 610 to bedetached from the nano-fingers 104 and released into the solution 706 asdenoted by the arrows 709.

Turning now to FIGS. 8A-8C, there are respectively shown diagrams 800,802, 804 of various stages of a method for forming 3-D nano-particleassemblies 610, according to an example. As shown in the diagram 800(FIG. 8A), the 3-D nano-particle assemblies 610 are depicted as beingimprinted into a sacrificial layer 806, which is provided on a baselayer 808. The base layer 808 may be formed of any suitable materialssuch as any of the materials listed above with respect to the substrate102. As such, and according to an example, the diagram 800 may depict astage following the formation of the 3-D nano-particle assemblies 610 inFIGS. 4A and 5A.

According to an example, the sacrificial layer 806 may be a fluidmaterial into which the 3-D nano-particle assemblies 610 may beinserted. The sacrificial layer 806 may be cured to trap the 3-Dnano-particle assemblies 610 inside the sacrificial layer 806. By way ofparticular example, the sacrificial layer 806 may include polymethylmethacrylate (PMMA).

As shown in the diagram 802 (FIG. 8B), the 3-D nano-particle assemblies610 may be separated from the nano-fingers 104 through relative movementof the substrate 102 and the nano-fingers 104 with respect to thesacrificial layer 806. According to an example, the substrate 102 andthe nano-fingers 104 may be moved as noted by the arrow 809 away fromthe sacrificial layer 806, while the sacrificial layer 806 is held inplace. Alternatively, the sacrificial layer 806 and the base layer 808may be moved away from the substrate 102 while the substrate 102 is heldin place. In any regard, the bond between the nano-fingers 104 and thesubstrate 102 may substantially be stronger than the bond, if any,between the nano-fingers 104 and the 3-D nano-particle assemblies 610.As such, when one of the substrate 102 and the sacrificial layer 806 ismoved away from the other, the 3-D nano-particle assembly 610 mayseparate or detach from the nano-fingers 104 as shown in FIG. 8B.

Following separation of the 3-D nano-particle assemblies 610 from thenano-fingers 104, a solution 810 that is to dissolve the sacrificiallayer 806 may be introduced onto the sacrificial layer 806. By way ofexample, the solution 810 may include a solvent, such as acetone,toluene, etc. The solution 810 is depicted in the diagram 804 (FIG. 8C),which depicts a stage of the method following the dissolving of thesacrificial layer 806. The diagram 804 also shows that the 3-Dnano-particle assemblies 610 have been released from the sacrificiallayer 806.

Turning now to FIGS. 9A-9C, there are respectively shown diagrams 900,902, 904 of various stages of a method for forming 3-D nano-particleassemblies 610, according to an example. As shown in the diagram 900(FIG. 9A), the 3-D nano-particle assemblies 610 are depicted as beingimprinted onto a sacrificial layer 906, which is provided on a baselayer 908. As such, and according to an example, the diagram 900 maydepict a stage following the formation of the 3-D nano-particleassemblies 610 in FIGS. 4A and 5A.

According to an example, the sacrificial layer 906 may include a metalmaterial, such as aluminum, titanium, etc. The sacrificial layer mayalso include a thin oxide layer on top to assist in the bindingchemistry. In addition, the 3-D nano-particle assemblies 610 may bebonded to the sacrificial layer 906 through use of a binding molecule,such as, 3-mercaptopropyltrimethoxysilane (MPTMS).

As shown in the diagram 902 (FIG. 9B), the 3-D nano-particle assemblies610 may be separated from the nano-fingers 104 through relative movementof the substrate 102 and the nano-fingers 104 with respect to thesacrificial layer 906. According to an example, the substrate 102 andthe nano-fingers 104 may be moved as noted by the arrow 909 away fromthe sacrificial layer 906, while the sacrificial layer 906 is held inplace. Alternatively, the sacrificial layer 906 and the base layer 908may be moved away from the substrate 102 while the substrate 102 is heldin place. In any regard, the bond between the nano-fingers. 104 and thesubstrate 102 may substantially be stronger than the bond, if any,between the nano-fingers 104 and the 3-D nano-particle assemblies 610.In addition, the bond between the 3-D nano-particle assemblies 610 andthe sacrificial layer 906 may substantially be stronger than the bond,if any, between the 3-D nano-particle assemblies 610 and thenano-fingers 104. As such, when one of the substrate 102 and thesacrificial layer 906 is moved away from the other, the 3-Dnano-particle assembly 610 may separate or detach from the nano-fingers104 as shown in FIG. 9B.

Following separation of the 3-D nano-particle assemblies 610 from thenano-fingers 104, a solution 910 that is to dissolve the sacrificiallayer 906 may be introduced onto the sacrificial layer 906. By way ofexample, the solution 910 may include an acid, such as HCl (hydrochloricacid), HF (hydrofluoric acid), etc. The solution 910 is depicted in thediagram 904 (FIG. 9C), which may depict a stage of the method followingthe dissolving of the sacrificial layer 906. The diagram 904 also showsthat the 3-D nano-particle assemblies 610 have been released from thesacrificial layer 906.

Although particular reference has been made in FIGS. 6A-9C to thedetachment of 3-D nano-particle assemblies 610 including the structuresdepicted in FIGS. 4A-5C, it should be understood that some of theconcepts discussed with respect to FIGS. 6A-9C may equivalently beapplied to detach the clusters 112 and the protective coatings 308depicted in FIGS. 3A-3C.

Following separation of the 3-D nano-particle assemblies 610 from thenano-fingers 104 in any of the manners discussed above, and in the caseof FIGS. 3A-3C, following the linking of multiple clusters 112, the 3-Dnano-particle assemblies 320, 610 may be employed in a sensing and/ortagging system. Particularly, for instance, the 3-D nano-particleassemblies 320, 610 may have trapped therein a reporter molecule, whichmay have been introduced between the SES elements 106 prior to partiallycollapsing of the nano-fingers 104 as discussed above. In addition,surfaces of the 3-D nano-particle assemblies 320, 610, for instance, theSES elements 106 and/or the protective coatings 308, may befunctionalized to preferentially bond to specific regions, e.g., targettissues/cells in a human body. Thus, for instance, the 3-D nano-particleassemblies 320, 610 disclosed herein may be employed to map the specificregions.

Although described specifically throughout the entirety of the instantdisclosure, representative examples of the present disclosure may haveutility over a wide range of applications, and the above discussion isnot intended and should not be construed to be limiting, but is offeredas an illustrative discussion of aspects of the disclosure.

What has been described and illustrated herein is an example along withsome of its variations. The terms, descriptions and figures used hereinare set forth by way of illustration only and are not meant aslimitations. Many variations are possible within the spirit and scope ofthe subject matter, which is intended to be defined by the followingclaims—and their equivalents—in which all terms are meant in theirbroadest reasonable sense unless otherwise indicated.

What is claimed is:
 1. A three-dimensional (3-D) nano-particle assemblycomprising: a first cluster of surface-enhanced spectroscopy (SES)elements; a second cluster of SES elements, wherein each of the firstand the second cluster of SES elements comprises, at least three SESelements attached to each other in a deterministic arrangement; amolecule trapped between the at least three SES elements; and aprotective coating on a first side of the cluster, wherein theprotective coating is functionalized to attach to a target molecule, andwherein the protective coating is not provided on a second side of thecluster that is opposite the first side of the cluster, and wherein thesecond side of the first cluster is bonded to the second side of thesecond cluster to form the 3-D nano-particle assembly.
 2. The 3-Dnano-particle assembly according to claim 1, wherein each of the firstcluster and the second cluster of SES elements is formed to have thedeterministic arrangement through deposition of the SES elements ontorespective tips of a plurality of nano-fingers, partial collapse of theplurality of nano-fingers toward adjacent ones of the plurality ofnano-fingers to cause the plurality of SES elements on adjacent groupsof the plurality of nano-fingers to come into sufficiently closeproximities to enable the SES elements to bond to each other and formthe cluster of SES elements, deposition of the protective coating,detachment of the cluster of SES elements from the plurality ofnano-fingers, and bonding of the first cluster of SES elements to thesecond cluster of SES elements through a linker molecule.
 3. The 3-Dnano-particle assembly according to claim 1, wherein the moleculecomprises a binding molecule that binds the SES elements in the firstcluster.
 4. The 3-D nano-particle assembly according to claim 1, whereinthe molecule comprises a reporter molecule.
 5. The 3-D nano-particleassembly according to claim 4, wherein the reporter molecule is one of aRaman tag and a fluorescence tag.
 6. The 3-D nano-particle assemblyaccording to claim 1, wherein the second side of the first cluster isbonded to the second side of the second cluster by a linker molecule. 7.The 3-D nano-particle assembly according to claim 1, wherein the secondcluster of SES elements has the same number of SES elements as the firstcluster of SES elements.